Self-Assembly of Toll-Like Receptor (TLR2/6) Agonist Lipidated Amino Acid or Peptide Conjugates: Distinct Morphologies and Bioactivities.

ABSTRACT: Toll-like receptor (TLR) agonists are of interest in immunotherapy and cancer vaccines. The most common agonists of TLR2 are based on Pam₂Cys or Pam₃Cys. In the former, two palmitoyl (Pam) fatty acids are linked to a glycerylcysteine motif by ester linkages. Pam₃Cys is analogous but contains an extra Pam group on the α-amine. Here, we compare the self-assembly in aqueous solution of the parent Pam₂CysOH and Pam₃Cys amino acid conjugates to that of Pam₂CysSK₄ and Pam₃CysSK₄ which are potent TLR2 agonists bearing the CysSK₄ peptide sequence. All four conjugates exhibit a critical aggregation concentration above which self-assembled structures are formed. We find through a combination

SUBMITTER: Castelletto V 

PROVIDER: S-EPMC12006960 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature